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H-Phg(4-OH)-OH is an endogenous metabolite.
Synonyms: L-p-Hydroxyphenylglycine; 4-Hydroxy-L-phenylglycine; Oxfenicinum
4.5
*For Research Use Only !
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CAS No. : | 32462-30-9 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | O=C(O)[C@@H](N)C1=CC=C(O)C=C1 |
Synonyms : |
L-p-Hydroxyphenylglycine; 4-Hydroxy-L-phenylglycine; Oxfenicinum
|
MDL No. : | MFCD00065932 |
InChI Key : | LJCWONGJFPCTTL-ZETCQYMHSA-N |
Pubchem ID : | 36143 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 20℃; for 12h;Inert atmosphere; | To a solution of (S)-2-amino-2-(4-hydroxyphenyl)acetic acid (15.0 g, 89.7 mmol, CAS 228 18-40-2) in methanol (100 mL) was added thionyl chloride (21.3 g, 179 mmol, 13 mL). The mixture was stirred at rt for 12 hours. The reaction mixture was concentrated under vacuum to give the title compound. LCMS: (ESj m/z (M+H) = 182.1, tR = 0.690. | |
With acetyl chloride; at 0 - 40℃; for 18h; | To a solution of 20 ML (230 mmol) of acetyl chloride in 400 ML of methanol at 0 °C was added 20 g (120 mmol) of (S)-4-HYDROXYPHENYLGLYCINE. The mixture was stirred at ambient temperature for 16 h, heated at 40 °C for 2 h, cooled and concentrated in vacuo. Water was added and the mixture was extracted with three portions of dichloromethane. The combined organic phase was washed with brine, dried over magnesium sulfate, and concentrated in vacuo to give the crude methyl ester. This material was dissolved in 400 mL of dichloromethane and 28.8 g (132 mmol) of di-tert-butyl dicarbonate, and 31.4 mL (180 mmol) OF N, N-DIISOPROPYLETHYLAMINE (DIEA) was added. The mixture was stirred at ambient temperature for 20 h, concentrated in vacuo, and dissolved in 400 ML of ethyl acetate. The organic phase was washed with sequentially with saturated sodium bicarbonate solution, water, and brine, dried over magnesium sulfate, and concentrated in vacuo. The crude solid was triturated with 200 mL of 1: 4 ether : hexane to give 30 g of the Boc carbamate which was dissolved in 300 ML of acetic acid. To the solution was added 2.2 g of platinum (IV) oxide and the reaction was shaken under an atmosphere of hydrogen (48 psi) for 2 h, filtered and concentrated in vacuo. The crude material was dissolved in ethyl acetate and washed sequentially with saturated sodium bicarbonate solution, water, and brine, dried over magnesium sulfate, and concentrated in vacuo. Purification by flash chromatography (silica gel, 20 to 40percent ethyl acetate in hexanes) afforded 8.83 g of the cis title compound: 1H NMR (400 MHz, CDC13) 8 5.05 (bd, 1H, J = 12HZ), 4.33-4. 27 (M, 1H), 4.05 (bs, 1H), 3.78 (s, 3H), 1.89-1. 78 (M, 2H), 1. 63-1. 38 (M, 16H). Continued elution gave 3.50 g of the trans title compound: H NMR (400 MHz, CDC13) 5 5.04 (bd, 1H, J = 12HZ), 4.30-4. 23 (M, 1H), 3.78 (s, 3H), 3.59-3. 51 (M, 1H), 2. 08-2. 00 (M, 2H), 1.79-1. 50 (M, 3H), 1.43 (s, 9H), 1.33-1. 04 (M, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydrogencarbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | To a solution of L-4-hydroxyphenylglycine (1.00 g, 5.98 mmol) and sodium hydrogencarbonate (2.50 g, 29.11 mmol) in a mixture of 1,4-dioxane (20 mL) and water (20 mL) was added di-tert-butyl dicarbonate (1.40 g, 6.58 mmol) at 0 0C, followed by stirring at room temperature for 18 hours. The organic portion of the solvent was evaporated, and the reaction mixture was partitioned between ethyl acetate (300 mL) and 0.5M aqueous hydrochloric acid (50 mL). The organic layer was separated and washed with 0.5M aqueous hydrochloric acid, water and brine, dried over sodium sulfate, filtered and the solvent concentrated to give (S)-2-(tert- butoxycarbonylamino)-2-(4-hydroxyphenyl)acetic acid (1.6 g, quantitative). 1H NMR (400 MHz, CDCl3): 8.80 (bs, IH), 7.12 (d, 2H), 6.62 (d, 2H), 5.80 (d, IH), 5.00 (d, IH), 1.22 (s, 9H). MS (EI) for CnHi7NO5: 266 (M-H). [00989] |
99% | In tetrahydrofuran; water; at 20℃; | 4-Hydroxy-L-phenylglycine (4.00 g, 23.93 mmol) and sodium bicarbonate (6.04 g, 71.80 mmol) was dissolved in water/tetrahydrofuran (70 mL/70 mL). The solution was cooled in an ice-bath and then di-tert-butyl dicarbonate (7.83 g, 35.90 mmol) was added into the solution. After stirring at room temperature overnight the mixture was washed with ether (50 mL). The aqueous portion was acidified to pH 4 with 2N HC1 and extracted with dichloromethane (3 x 100 mL). The organic portion was washed with saturated sodium chloride (60 mL) and dried over anhydrous sodium sulfate. The organic portion was filtered, concentrated, and dried under high vacuum to give 6.35 g product as a white solid (yield: 99%). NMR (500 MHz, CD3OD): delta 7.22 (d, 2H), 6.77 (d, 2H), 5.07 (br, 1 H), 1.45 (s, 9H); MS (EI) for C,3Hi7N05: 266 (MH"). |
86% | With triethylamine; In tetrahydrofuran; water; at 0℃; for 18h; | To a solution of (S)-2-amino-2-(4-hydroxyphenyl)acetic acid (2.00 g, 11.96 mmol) and Et3N (1.67 mL, 11.96 mmol) in THF (30 mL) and H2O (30 mL) at 0 C. was added di-tert-butyl dicarbonate (2.61 g. 11.96 mmol). The solution was stirred at 0 C. for 18 hours and then concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 5% H3PO4 aqueous solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound as a light colored solid. The crude material was taken on directly to the next step. (2.85 g, 86% yield) MS (ESI+) m/z=290 (M+Na)+ |
With potassium carbonate; In tetrahydrofuran; water; at 0 - 20℃; for 16h; | Preparation 14: (.S)-ferf-Butoxycarbonylamino-(4-hydroxyphenyl)acetic acid; (5)-4-Hydroxyphenylglycine (10.00 g, 59.8 mmol) was added to H2O (50 mL) and THF (50 mL) at O0C under argon. K2CO3 (16.40 g, 119.8 mmol) and di-ferf-butyl dicarbonate (14.4 g, 66.0 mmol) were added and the reaction was stirred at ambient temperature for 16 h. The THF was removed in vacuo, then the aqueous layer was extracted with EtOAc (50 mL), acidified to pH 4 with citric acid and further extracted with EtOAc (2 X 50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo, azeotroping several times with DCM to afford the title compound: RT = 2.55 min, m/z (ES+) = 268.1 [M + H]+. | |
With sodium hydrogencarbonate; In water; acetone; | To a solution of 4-hydroxyphenylglycine (12 g, 71.860 mmol) in a 1:1 mixture of acetone and water was addeddi-tert-butyldicarbonate (16.5 mL, 71.8 mmol, 1 eq) andsodium bicarbonate (6.03 g, 0.11 mol, 1.5 eq). The solutionwas allowed to stir overnight, and then was quenched with theaddition of citric acid (pH 3) to pH 4. The aqueous layer was65 then extracted 2x with EtOAc and the combined organiclayers were washed with brine, dried over Na2S04 and concentratedto a white foam. The crude material (18.43 g, 69mmol (assumed)) was used without further purification bydissolving it in anhydrous DMF and treating sequentiallywith triethylamine (12.6 mL, 75.9 mmol, 1.3 eq), HOBT(9.32 g, 69 mmol, 1 eq) andAla-OMe HCl (9.63 g, 69 mmol,1 eq). The solution was then cooled to oo C. and EDC (19.55 5g, 0.1 mol, 1.5 eq) was added in one portion. The reaction wasallowed to warm to room temperature and stirred overnight.Water and EtOAc were added, the aqueous layer wasextracted 3x, and the combined organic layers were washedwith brine, dried over Na2S04 and concentrated. The residue 10was purified by flash chromatography (6% MeOH, 0.6%AcOH in DCM) to give a clear residue (17.82 g, 71% yield).Rf=0.39 (7% MeOH in DCM). 1H NMR (CDC13 , 600 MHz)o (ppm) 7.11 (d, 1=8.4 Hz, 2H), 6.64 (d, 1=8.4 Hz, 2H), 6.51 15(brd, 1=6.6 Hz, lH), 5.71 (brs, lH), 5.07 (brs, lH), 4.57-4.52(m, 1H),3.69(s,3H), 1.42-1.40(m, 12H). 13CNMR(CDC13 ,600 MHz) o (ppm) 173.2, 170.5, 156.6, 155.4, 129.0, 128.7(2C), 116.1 (2C), 80.5, 58.2, 52.7, 48.5, 28.4 (3C), 18.4. IR(film)vmax=1655, 1512,1450,1365,1215,1157,1049 cm-1. 20ESI HRMS calcd for [(M+NatJ C17H24N20 6 : 375.1526.found: 375.1532. | |
With sodium hydrogencarbonate; In water; acetone; at 25℃; | To a stirred mixture of (S)-2-amino-2-(4-hydroxyphenyl)acetic acid (100 g, 0.6 mol, 1 eq) in a mixture of acetone (400 mL) and water (400 mL) was added di-tert-butyl dicarbonate (130.5 g, 0.6 mol, 1 eq) and NaHCO3 (75.4 g, 0.9 mol, 1.5 eq). The mixture wasallowed to stir at 25 C overnight. After HPLC showed the reaction was complete, the mixture was acidified with 5% citric acid (pH 3). The mixture was filtered and the filter cake was washed with water, then dried to give (S)-2-((tert-butoxycarbonyl)amino)-2-(4- hydroxyphenyl)acetic acid (140 g, 87.5%). The crude product was used directly without further purification. | |
With sodium hydrogencarbonate; In water; acetone; at 25℃; | To a stirred mixture of (S)-2-amino-2-(4-hydroxyphenyl)acetic acid (100 g, 0.6 mol, 1 eq) in a mixture of acetone (400 mL) and water (400 mL) was added di-tert-butyl dicarbonate (130.5 g, 0.6 mol, 1 eq) and NaHCO3 (75.4 g, 0.9 mol, 1.5 eq). The mixture wasallowed to stir at 25C overnight. After HPLC showed the reaction was complete, the mixture was acidified with 5% citric acid (pH 3). The mixture was filtered and the filter cake was washed with water, then dried to give (S)-2-((tert-butoxycarbonyl)amino)-2-(4- hydroxyphenyl)acetic acid (140 g, 87.5%). The crude product was used directly without further purification. | |
Boc anhydride (1.6 g, 7.2 mmol) in 10 ml THF was added dropwise to an ice-cooled stirring solution of 4-hydroxy-L-phenylglycine (1.0 g, 6 mmol) and NaHCtheta3 (1.0 g, 12 mmol) in 10 ml water. After complete addition, solution was warmed to room temp and stirred overnight. THF was evaporated off and 10 ml water was added. The aqueous layer was extracted twice with 20 ml ethyl acetate and the aqueous layer was acidified to pH 3 with aqueous citric acid. The aqueous layer was extracted twice with 25 ml ethyl acetate and organic layers combined. The organic layer was washed twice with brine and once with water, dried over MgStheta4 and concentrated to yield 1.5 g Boc-4-hydroxy-L-phenylglycine (Boc-Phg(4-OH)). The protected amino acid was a single peak with the correct mass by LCMS and was used without further purification. Calculated mass 267.3, found 268.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With thionyl chloride; at 0 - 75℃; for 2h; | General procedure: The methyl-esterification reaction of L-phenylalanine.To a suspension of L-phenylalanine (1 g, 6.05 mmol, 1.0 equiv) inmethanol (25 mL) cooled to 0 C was added thionyl chloride(475 mL, 6.66 mmol, 1.5 equiv) slowly. After 10 min, the reactionmixture was heated to 75 C to reflux for 2 h. After completion(monitored by TLC), the solvent was removed in vacuo, and at thistime, a white solid was formed methyl L-phenylalaninate hydrochloride(1.23 g, quantitative yield). |
Tags: 32462-30-9 synthesis path| 32462-30-9 SDS| 32462-30-9 COA| 32462-30-9 purity| 32462-30-9 application| 32462-30-9 NMR| 32462-30-9 COA| 32462-30-9 structure
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